This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The active zones at the presynaptic terminals are located at the center of the synaptic vesicle exocytic zone, promote synaptic vesicles docking, and provide the precise registry between pre- and postsynaptic specializations. Active zones display morphologically distinct ultrastructures. By screening for C. elegans mutants with altered synaptic vesicles distribution, we discovered that the conserved protein SYD-2 is a key regulator of active zone assembly. In syd-2 lost-of-function mutants, active zones exhibit a fragmented appearance, causing diffused localization of synaptic vesicles. Recently, we uncovered an unusual syd-2 gain-of-function mutation that is able to promote synapse assembly in the absence of several upstream regulators. Using this mutation, we have dissected the complex interactions among active zone proteins. This study provides insight into the molecular network of presynaptic active zone assembly.